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Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population


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Lewis, JP, Riaz, M, Xie, S, Polekhina, G, Wolfe, R, Nelson, M ORCID: 0000-0001-9941-7161, Tonkin, AM, Reid, CM, Murray, AM, McNeil, JJ, Shuldiner, AR and Lacaze, P 2020 , 'Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population' , Clinical Pharmacology and Therapeutics , pp. 1-27 , doi: 10.1002/cpt.1959.

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The platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherothrombotic cardiovascular events is less clear, with limited evidence from large trials. Here, we tested association of rs12041331 with cardiovascular events and aspirin use in a randomized trial population of healthy older individuals. We undertook post-hoc analysis of N=13,547 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, median age 74 years. Participants had no previous diagnosis of atherothrombotic cardiovascular disease at enrolment, and were randomized to either 100 mg daily low-dose aspirin or placebo for median 4.7 years follow-up. We used Cox proportional hazard regression to model the relationship between rs12041331 and the ASPREE primary cardiovascular disease endpoint (CVD), and composites of major adverse cardiovascular events (MACE) and ischaemic stroke (STROKE); and bleeding events; major hemorrhage (MHEM) and intracranial bleeding (ICB). We performed whole-population analysis using additive and dominant inheritance models, then stratified by treatment group. Interaction effects between genotypes and treatment group were examined. We observed no statistically significant association (PPEAR1 rs12041331 is not associated with cardiovascular events in response to low-dose aspirin in a healthy elderly population.

Item Type: Article
Authors/Creators:Lewis, JP and Riaz, M and Xie, S and Polekhina, G and Wolfe, R and Nelson, M and Tonkin, AM and Reid, CM and Murray, AM and McNeil, JJ and Shuldiner, AR and Lacaze, P
Keywords: genetics, aspirin, platelet aggregation, cardiovascular disease
Journal or Publication Title: Clinical Pharmacology and Therapeutics
Publisher: Mosby
ISSN: 0009-9236
DOI / ID Number: 10.1002/cpt.1959
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2020 American Society for Clinical Pharmacology and Therapeutics

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